1132659-99-4

Upstream product

• 584-02-1 2-pentanol 
• 1151665-76-7 ethyl (1S,5R,6S)-5-methanesulfonyloxy-7-azabicyclo[4.1.0]hept-2-ene-3-carboxylate 
• 1132659-97-2 (3R,4S,5R)-4-[(diethoxyphosphoryl)amino]-3-(1-ethylpropoxy)-5-(methanesulfonyloxy)cyclohex-1-enecarboxylic acid ethyl ester 
• 108-24-7 acetic anhydride 
• 1151665-75-6 (3R,4S,5R)-3-azido-4,5-bis-methanesulfonyloxy-cyclohex-1-enecarboxylic acid ethyl ester 
• 1132659-98-3 (3R,4S,5R)-4-amino-3-(1-ethyl-propoxy)-5-methanesulfonyloxy-cyclohex-1-enecarboxylic acid ethyl ester 
• 1132659-94-9 (3R,4S,5R)-3,4,5-tris-methanesulfonyloxy-cyclohex-1-enecarboxylic acid ethyl ester 
• 1132659-96-1 (1S,5R,6S)-7-(diethoxy-phosphoryl)-5-methanesulfonyloxy-7-aza-bicyclo[4.1.0]hept-2-ene-3-carboxylic acid ethyl ester 
• 1376576-18-9 ethyl (4R)-4-((2S,3R)-3-(hydroxymethyl)oxiran-2-yl)-4-(methoxymethoxy)-2-methylenebutanoate 
• 1376576-15-6 ethyl (4R)-4-((2S,3R)-3-((tert-butyldimethylsilyloxy)methyl)oxiran-2-yl)-4-(methoxymethoxy)-2-methylenebutanoate 
• 1376576-12-3 ethyl (4R)-4-((2S,3R)-3-((tert-butyldimethylsilyloxy)methyl)oxiran-2-yl)-4-hydroxy-2-methylenebutanoate 
• 1401454-81-6 (2R,3S)-tert-butyl 2-((tert-butyldimethylsilyloxy)methyl)-3-((R)-3-(ethoxycarbonyl)-1-hydroxybut-3-en-1-yl)aziridine-1-carboxylate 
• 1401454-88-3 ethyl (3R,4S,5R)-4-(tert-butoxycarbonylamino)-3-(1-ethylpropoxy)-5-(methanesulfonyloxy)cyclohex-1-ene-1-carboxylate 
• 1401454-87-2 ethyl (1S,5R,6S)-7-(tert-butoxycarbonyl)-5-(methanesulfonyloxy)-7-azabicyclo[4.1.0]hept-2-ene-3-carboxylate 

Downstream Products

• 204255-06-1 oseltamivir 
• 1151665-78-9 C₁₄H₂₀O₃ 
• 1402431-91-7 ethyl (3R,4R,5R)-4-acetylamino-5-amino-3-(pentan-3-yloxy)cyclohex-1-ene-1-carboxylate 
• 204255-11-8 oseltamivir phosphate 
• 1191921-01-3 (3R,4R,5S)-4-acetylamino-5-acetylamino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylic acid ethyl ester 
• 1588477-09-1 ethyl (3R,4R,5S)-4-acetamido-5-(1-(benzyloxycarbonyl)-2-methylguanidino)-3-(pentan-3-yloxy)cyclohex-1-enecarboxylate 
• 1588477-08-0 (3R,4R,5S)-ethyl 4-acetamido-5-(3-((benzyloxy)carbonyl)thioureido)-3-(pentan-3-yloxy)-cyclohex-1-enecarboxylate 
• 1192537-55-5 (3R,4R,5S)-5-[[(1Z)-[[(tert-butoxy)carbonyl]amino]([[(tert-butoxy)carbonyl]imino])methyl]amino]-4-acetylamino-3-(pent-3-yloxy)cyclohexyl-1-ene-1-carboxylic acid 

Relevant academic research and scientific papers

FLOW SYNTHESIS PROCESS FOR THE PRODUCTION OF OSELTAMIVIR

This invention provides for a flow synthesis process for producing Oseltamivir and pharmaceutically acceptable salts thereof from shikimic acid in particular but not exclusively to a flow synthesis process for producing Oseltamivir phosphate from shikimic acid in a nine-step flow synthesis that provides for superior reaction times and product yields compared to known methods.

Method for preparing oseltamivir phosphate by azide process

The invention belongs to the field of pharmaceutical chemicals, and particularly relates to a method for preparing oseltamivir phosphate by an azide process. The method comprises the following steps:reacting a compound shown in a formula (III) with sodium azide and ammonium chloride, opening a nitrogen heterocyclic ring, performing acetylation, reducing an azide group, removing tert-butyl, salifying with phosphoric acid, and purifying to obtain pure oseltamivir phosphate shown in a formula (I). According to the method, diallylamine with strong corrosivity and expensive palladium acetate do not need to be used so that the enterprise cost is reduced.

The hydrophobic side chain of oseltamivir influences type A subtype selectivity of neuraminidase inhibitors

Neuraminidase, which plays a critical role in the influenza virus life cycle, is a target for new therapeutic agents. The study of structure–activity relationships revealed that the C-5 position amino group of oseltamivir was pointed to 150-cavity of the neuraminidase in group 1. This cavity is important for selectivity of inhibitors against N1 versus N2 NA. A serial of influenza neuraminidase inhibitors with the oseltamivir scaffold containing lipophilic side chains at the C-5 position have been synthesized and evaluated for their influenza neuraminidase inhibitory activity and selectivity. The results indicated that compound 13o (H5N1 IC50?=?0.1?±?0.04?μm, H3N2 IC50?=?0.26?±?0.18?μm) showed better inhibitory activity and selectivity against the group 1 neuraminidase. This study may provide a clue to design of better group 1 neuraminidase inhibitors.

PROCESS FOR THE PREPARATION OF OSELTAMIVIR AND METHYL 3-EPI-SHIKIMATE

The present invention discloses high yielding enantioselective process for synthesis of Oseltamivir from readily available starting material, cis-1,4-butene diol. The process features incorporation of chirality using sharpless asymmetric epoxidation (AE) and diastereoselective Barbier allylation and construction of cyclohexene carboxylic acid ester core through a ring closing metathesis (RCM) reaction. Further also disclosed herein is synthesis of (?)-methyl 3-epi-shikimate.

Oseltamivir analogues bearing N-substituted guanidines as potent neuraminidase inhibitors

A series of oseltamivir analogues bearing an N-substituted guanidine unit were prepared and evaluated as inhibitors of neuraminidases from four strains of influenza the two most potent analogues identified contain relatively small N-guanidine substituents (N-methyl and N-hydroxyl) and display enhanced inhibition with IC50 values in the low nanomolar range against neuraminidases from wild-type and oseltamivir-resistant strains. Potential advantages of including the N-hydroxyguanidine moiety in neuraminidase inhibitors are also discussed.

PROCESS FOR THE PREPARATION OF OSELTAMIVIR AND METHYL 3-EPI-SHIKIMATE

The present invention discloses high yielding enantioselective process for synthesis of Oseltamivir from readily available starting material, cis-1,4-butene diol.The process features incorporation of chirality using sharpless asymmetric epoxidation(AE) and diastereoselective Barbier allylation and construction of cyclohexene carboxylic acid ester core through a ring closing metathesis (RCM) reaction. Further also disclosed herein is synthesis of (-)-methyl 3-epi-shikimate.

Facile method for the synthesis of oseltamivir phosphate

A ten-step scheme for the preparation of an antiviral agent, ethyl (3R,4R,5S)-4-acetylamino-5-amino-3-(pent-3-yloxy)cyclohex-1-enecarboxylate phosphate, from (-)-shikimic acid was studied. The main parameters of the synthesis were determined and the optimal conditions for the preparation of the intermediate compounds were selected. The total yield of oseltamivir phosphate calculated based on (-)-shikimic acid was 27%.

Synthesis of the anti-influenza agent (-)-oseltamivir free base and (-)-methyl 3-epi-shikimate

A new enantioselective synthesis of the anti-influenza agent (-)-oseltamivir free base (7.1% overall yield; 98% ee) and (-)-methyl 3-epi-shikimate (16% overall yield; 98% ee) has been described from readily available raw materials. Sharpless asymmetric epoxidation and diastereoselective Barbier allylation of an aldehyde are the key reactions employed in the incorporation of chirality, while the cyclohexene carboxylic ester core was constructed through a ring closing metathesis reaction.

A new efficient synthesis of oseltamivir phosphate (Tamiflu) from (-)-shikimic acid

New synthesis of oseltamivir phosphate was accomplished in 9 steps with a 27% overall yield from a readily available (-)-shikimic acid. Selective ring opening reaction of ketal and azide Mitsunobu reaction for facile replacement of a hydroxyl group by the N3 group at the C-3 position of (3R,4R,5R)-ethyl 4-hydroxy-5-(methoxymethoxy)-3-(pentan-3-yloxy)cyclohex-1-enecarboxylate 4 and at the C-4 position of (3R,4S,5R)-ethyl 4-acetamido-5-hydroxy-3-(pentan-3-yloxy) cyclohex-1-enecarboxylate 7 successfully served as the key steps.

Synthesis of (-)-oseltamivir phosphate (tamiflu) starting from cis-2,3-bis(hydroxymethyl)aziridine

Oseltamivir phosphate (Tamiflu) has been synthesized from cis-2,3-bis(hydroxymethyl)aziridine. After protection of the cis-2,3-bis(hydroxymethyl)aziridine with a Boc group, desymmetrization provided a chiral aziridine, which was a key intermediate to install the required stereogenic center containing a nitrogen atom. Allylation and ring closing metathesis are the key reactions to obtain the cyclic product that was successfully converted to the desired oseltamivir phosphate.